Vertebral hemangioma - the current radiation therapy perspective.

Vertebral hemangiomas are benign tumors of the spine, most often detected incidentally and on other instances, when signs and symptoms of the disease arise. About 10% of the population are affected worldwide with a female to male ratio of 2:1. The majority of these cases are asymptomatic and no intervention is generally required. Less often, back pain and neurological deficit may occur. Such hemangiomas are termed aggressive by the Enneking staging and warrant treatment. In this review, staging and diagnostics are discussed in detail followed by treatment options. Treatment options entail Surgical intervention, Percutaneous ethanol injection, radiofrequency ablation and Radiation Therapy. There are no set guidelines on preference or order of the treatment options. Further, in this review, studies favouring Radiation therapy regimes and their outcomes are elaborated.

Role of stereotactic body radiotherapy for inferior vena cava tumour thrombus in hepatocellular carcinoma.

INTRODUCTION: To evaluate the role of stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) patients with inferior vena cava tumour thrombus (IVCTT) who are not suitable for other loco-regional therapies. METHODS: This is an observational retrospective study done between May 2020 and April 2022. The data of 17 patients who underwent SBRT were collected. Patients of Child-Pugh score (CPS) A5-B7 and along with a liver reserve of ≥700 cc were included. Local control (LC), overall survival (OS) and adverse events including hepatic decompensation were carefully recorded. RESULTS: In the cohort, the tumour thrombus was extended to the right atrium in nine (52.9%) patients, and regional nodal and lung were found in 60% and 31.4% of patients respectively. The median gross tumour volume (GTV) was 745 cc (107-1,650 cc). The median SBRT dose prescription was 35 Gy (25-45 Gy) in 5-10 fractions. At 6 months, LC and OS were 80% and 75% respectively. On multivariate analysis, an ALBI score >-2.36 was found to be the predictor for the poor OS. Post-SBRT, a change in CPs by 2 points was observed in one patient (5.9%) which was managed conservatively. Post-radiation, improvement in pain and discomfort was observed in 92.3% and 87% of patients, respectively and bone metastasis related pain was also resolved. CONCLUSION: Stereotactic body radiotherapy is a safe and feasible option for HCC patients with IVC and right atrium tumour thrombosis. It not only improves the quality of life but also results in good LC and OS with acceptable toxicity. SBRT should be considered in a multidisciplinary fashion for patients presenting with tumour thrombosis extending to IVC and the right atrium.

Role of palliative SBRT in barcelona clinic liver cancer-stage C hepatocellular carcinoma patients.

OBJECTIVE: To evaluate the role of palliative stereotactic body radiation therapy (SBRT) in Barcelona Clinic Liver Cancer stage­C (BCLC-C) hepatocellular carcinoma (HCC) patients who are not suitable for other loco-regional therapies. MATERIALS AND METHODS: It is an observational retrospective study done between May 2020 and September 2021. The data were collected from 35 patients of advanced HCC who underwent SBRT. Patients of Child Pugh status (CPs) A5-B7 and with a liver reserve of ≥ 700cc were included. Local control (LC), overall survival (OS) and adverse events including decompensation were carefully recorded. RESULTS: In the cohort, Portal vein and IVC tumor thrombosis were present in 33 (94.3%) and 8 (22.85%) patients, respectively. Lung and nodal metastasis were found in 11 (31.4%) and 21 (60%) of patients, respectively. The median gross tumor volume (GTV) was 563cc (range 80-1925cc). The median SBRT dose prescription was 35 Gy (range 25-40 Gy) in 5-10 fractions. Post radiation therapy, there was improvement in pain and discomfort in 24 out of 29 (82.75%) and 18 out of 23 (78%) patients respectively. Also bone metastasis related pain was improved in all 3 (100%) patients. One year LC, and OS were 80% and 30% respectively. On multivariate analysis, the GTV volume > 750cc and PIVKA-II > 8000 mAU/ml remained the predictor factor for poor OS. Post SBRT, change in child-pugh score by 1 point was observed in 7 patients (20%) which was managed conservatively. CONCLUSION: SBRT is a safe and feasible option for BCLC­C HCC. It not only improves the quality of life by symptom control but also results in good LC and OS with acceptable toxicity. SBRT should be considered in a multidisciplinary fashion for patients presenting with advanced HCCs.

Degree of reduction in normal liver complication probability from free-breathing to breath-hold liver SBRT: a dose-escalation strategy using radiation dose-volume effect.

Introduction. This study aimed to analyze the degree of reduction in normal liver complication probability (NTCP) from free-breathing (FB) to breath-hold (BH) liver SBRT. The effect of the radiation dose-volume on the mean liver dose (MLD) was also analyzed due to dose prescription, normal liver volume (NLV), and PTV.Materials and Methods. Thirty-three stereotactic body radiation therapy (SBRT) cases of hepatocellular carcinoma were selected, retrospectively. For FB, the treatments were planned on average intensity projection scan (CTavg), and patient-specific internal target volume (ITV) margins were applied. To simulate the BH treatment, computed tomography (CT) scan correspond to the 40%-50% of the respiratory cycle (CT40%-50%) was chosen, and an appropriate intrafraction margin of 2 mm, 1.5 mm, and 1.5 mm were given in craniocaudal (CC), superior-inferior (SI), and lateral direction to generate the final iGTV. As per RTOG 1112, all organs at risk (OAR's) were considered during the optimization of treatment plans. NTCP was calculated using LKB fractionated model. Multivariate regression analysis was performed to see the effect of EQD2Gy, NLV, and PTV on MLD2Gy.Results.A significant dosimetric difference was observed in the normal liver (liver-ITV/iGTV). A reduction of 1.7% in NTCP was observed from FB to BH technique. The leverage of dose escalation is more in BH because MLD2Gycorresponds to 5%, 10%, 20%, and 50% NTCP was 0.099 Gy, 0.41 Gy, 1.21 Gy, and 3.432 Gy more in BH as compared to FB technique. In MVRA, the major factor which was attributed to a change in MLD2Gyis EQD2Gy. Conclusion. From FB to BH technique, a significant reduction in NTCP was observed. The dose prescription is a major factor attributed to the change in MLD2Gy. Advances in knowledge: If feasible, prefer BH treatment either for tumor dose escalation or for the reduction in NTCP.

Efficacy and toxicity of SBRT in advanced hepatocellular carcinoma with portal vein tumor thrombosis - a retrospective study.

BACKGROUND: The purpose of this study was to evaluate the outcome of stereotactic body radiation therapy (SBRT) in patients of unresectable hepatocellular carcinoma (HCC ) complicated with portal vein tumor thrombosis (PVTT) who are also unsuitable for other locoregional therapies. MATERIALS AND METHODS: Between May 2018 and January 2020, twenty-nine patients with advanced unresectable HCC s, treated with SBRT, were enrolled in this retrospective audit. Patients of Child status A5-B7 and with healthy liver volume, ≥ 700 ccs were treated. Local control (LC), overall survival (OS), progression-free survival (PFS), PVTT opening rate, and effect of prognostic factors were analyzed. RESULTS: The median tumor diameter was 8.6 cm (5-14), and the median tumor volume was 275 cc (151-1196). The median SBRT dose prescription was 48 Gy in 6 fractions (32-50 Gy in 5-6 fractions). The median follow up was eight months (1-20), 1-year local control, progression-free survival, and overall survival were 95%, 53.4%, and 60%, respectively. Overall rate of grade III toxicity was less than 5%, and the most common toxicity was lymphocytopenia. Tumors of more than 350cc had worse OS and PFS when compared to tumors < 350 cc (median OS and PFS of tumors > 350 cc was 4 months and two months, p = .01 and .003, respectively). A total of fifteen patients progressed with the disease and the median time to progression was two months [1-4]. CONCLUSION: SBRT is safe and provides excellent local control in advanced HCC complicated with PVTT. The out of field failure pattern and time to failure in these patients highlights the need for adjuvant systemic therapy after completion of local treatment. Our data warrant the need for multimodality trials in this patient cohort.

Dosimetric impact of contrast-enhanced 4d computed tomography for stereotactic body radiation therapy of hepatocelluar carcinoma.

BACKGROUND: A purpose of the study was to investigate the dosimetric impact of contrast media on dose calculation using average 4D contrast-enhanced computed tomography (4D-CECT) and delayed 4D-CT (d4D-CT) images caused by CT simulation contrast agents for stereotactic body radiation therapy (SBRT) of liver cases. MATERIALS AND METHODS: Fifteen patients of liver SBRT treated using the volumetric modulated arc therapy (VMAT) technique were selected retrospectively. 4D-CECT, and d4D-CT were acquired with the Anzai gating system and GE CT. For all patients, gross target volume (GTV) was contoured on the ten phases after rigid registration of both the contrast and delayed scans and merged to generate internal target volume (ITV) on average CT images. Region of interest (ROI) was drawn on contrast images and then copied to the delayed images after rigid registration of two average CT datasets. The treatment plans were generated for contrast enhanced average CT, delayed average CT and contrast enhanced average CT with electron density of the heart overridden. RESULTS: No significant dosimetric difference was observed in plans parameters (mean HU value of the liver, total monitor units, total control points, degree of modulation and average segment area) except mean HU value of the aorta amongst the three arms. All the OARs were evaluated and resulted in statistically insignificant variation (p > 0.05) using one way ANOVA analysis. CONCLUSIONS: Contrast enhanced 4D-CT is advantageous in accurate delineation of tumors and assessing accurate ITV. The treatment plans generated on average 4D-CECT and average d4D-CT have a clinically insignificant effect on dosimetric parameters.

Dosimetric analysis of cervical cancer stage IIB patients treated with volumetric modulated arc therapy using plan uncertainty parameters module of Varian Eclipse treatment planning system.

Introduction. The present study aims to investigate the dosimetric and radiobiological impact of patient setup errors (PSE) on the target and organs at risk (OAR) of the cervix carcinoma stage IIB patients treated with volumetric-modulated arc therapy (VMAT) delivery technique using plan uncertainty parameters module of Varian Eclipse treatment planning system and in-house developed DVH Analyzer program.Materials and Methods. A total of 976 VMAT plans were generated to simulate the PSE in the base plan that varies from -10 mm to 10 mm in a step size of 1 mm in x- (lateral), y- (craniocaudal), and z- (anteroposterior) directions. The different OAR and tumor (PTV) volumes were delineated in each case. Various plan quality metrics, such as conformity index (CI) and homogeneity index (HI), as well as radiobiological quantities, such as tumor control probability (TCP) and normal tissue control probability (NTCP), were calculated from the DVH bands generated from the cohort of treatment plans associated with each patient case, using an in-house developed 'DVH Analyzer' program. The extracted parameters were statistically analyzed and compared with the base plan's dosimetric parameters having no PSE.Results. The maximum variation of (i) 2.4%, 21.5%, 0.8%, 2.5% in D2ccof bladder, rectum, small bowel and sigmoid colon respectively; (ii) 19.3% and 18.9% in Dmaxof the left and right femoral heads (iii) 16.9% in D95%of PTV (iv) 12.1% in NTCP of sigmoid colon were observed with change of PSE in all directions. TCP was found to be considerably affected for PSEs larger than 4 mm in x+, y+, z+directions and 7 mm in x-, y-and z-directions, respectively.Conclusion. This study presents the effect of PSE on TCP and NTCP for the cervix carcinoma cases treated with VMAT technique and also recommends daily image guidance to mitigate the effects of PSE.

Impact of dose heterogeneity in target on TCP and NTCP for various radiobiological models in liver SBRT: different isodose prescription strategy.

INTRODUCTION: The impact of dose heterogeneity within the tumor on TCP and NTCP was studied using various radiobiological models. The effect of the degree of heterogeneity index (HI) on TCP was also analyzed. MATERIALS AND METHODS: Thirty-seven pre-treated liver SBRT cases were included in this study. Two different kinds of treatment techniques were employed. In both arms, the prescribed dose was received by 95% of the PTV. Initially, the inhomogeneous treatment plans (IHTP) were made in which the spatial change of dose within the PTV was high and the maximum dose within the PTV can go up to 160%. Subsequently, in another arm, homogeneous treatment plans (HTP) were generated in which PTV was covered with the same prescription isodose and the maximum dose can go up to 120%. As per RTOG 1112, all organs at risk (OAR's) were considered while optimization of the treatment plans. TCP was calculated using the Niemierko and Poisson model. NTCP was calculated using the Niemierko and LKB fractionated model. RESULTS: For the IHTP, TCP was decreasing as 'a' value decreased in the Niemierko model whereas, for HTP, TCP was found to be the same. NTCP of the normal liver was less in IHTP as compared to HTP, and the Niemierko model overestimates the NTCP as compared to LKB fractionated model. NTCP for all other OAR's was <1% in both kinds of treatment plans. CONCLUSION: IHTP is found to be clinically better than HTP because NTCP of the normal liver was significantly less and TCP was more for certain 'a' values of the Niemierko model and the Poisson model. There is not any effect of HI on TCP was observed. Advances in knowledge: IHTP could be used clinically because of the dose-escalation and subsequently, leads to an increase in the TCP.

Interplay effect modeling in stereotactic body radiotherapy treatment of liver cancer using volumetric modulated arc therapy.

To model the interplay effect and minimize it by a selection of optimum parameters value using a predictive model for SBRT of liver cancers. Ten cases of liver tumors treated with the VMAT technique were selected retrospectively. The dosimetric error due to the interplay effect was measured with a micro ionization chamber (0.015cm3) in a Quasar phantom simulating the moving tumor. The interplay effect dependent parameter's viz. patient breaths per minute, the amplitude of respiration, fractional dose (FD), plan complexity due to different energies (Relative degree of modulation), degree of modulation due to a different level of dose optimization constraints, and dose rate (DR) were measured. For the predictive model, mathematical equations were modeled in python from 300 combinations of proposed parameters using multivariate regression analysis. It was observed that the dose variation reduced from -8.44% to -5.16% for change in the BPM values from 7 to 31 and similarly for amplitude, the dose variation reduced from -9.44% to -4.93% for change in amplitude value from 16 mm to 2 mm. The DR and FD have a prominent effect with R2 values of 0.990 and 0.880 respectively. The calculated mean square errors of equations excluding amplitude for the predictive model were 0.90 and 0.82 whereas those for equations excluding BPM were 1.31 and 1.41 for 6 MV and 10 MV beams respectively. The values of the parameters can be prospectively optimized by the use of the predictive model according to clinical situations, so dose variation can be minimized.

Efficiency of a novel non-monotonic segmented leaf sequence delivery of Varian MLC for non-split IMRT fields.

AIM: Development of bidirectional non-monotonic segmented leaf sequence (NSLS) MLC delivery technique compatible with Varian MLC for non-split IMRT fields reducing total monitor units (TotalMU) and the number of segments (NS) simultaneously and assessment of its efficiency using a plan scoring index (PSI). MATERIALS AND METHODS: The optimal fluence of IMRT plans of ten patients of lung carcinoma, calculated using Eclipse TPS version 11.0 (Varian Medical Systems, Palo Alto, CA, USA), was used to generate the segmented MLC fields using our newly developed equally spaced (ES) reducing level and NSLS algorithms in MATLAB® version 2011b for 6-10 intensity levels. These MLC fields were imported into the plans with the same field setup and the final dose was recalculated. The results were compared with those of commercially available multiple static segments (MSS) leaf motion calculation (LMC) algorithm and few previously published algorithms. Plan scoring index (PSI) and degree of modulation (DoM) was calculated to compare the quality of different plans for the same patient. RESULTS: The average differences in TotalMU and NS with respect to MSS algorithm are -3.80% and -14.28% for the NSLS algorithm, respectively. The calculated average PSI and DoM is 0.75, 2.51 and 0.91, 2.41 for the MSS and NSLS algorithms, respectively. CONCLUSIONS: IMRT plans generated using the NSLS algorithm resulted in the best PSI, DoM values among all the leaf sequencing algorithms. Our proposed NSLS algorithm allows bidirectional delivery in Varian medical linear accelerator which is not commercially available. NSLS algorithm is efficient in reducing the TotalMU and NS with equivalent plan quality as that of MSS.

Voxel based evaluation of sequential radiotherapy treatment plans with different dose fractionation schemes.

OBJECTIVE: This study presents a methodology for voxel-based evaluation of two phase sequential radiotherapy treatment plans having conventional dose scheme in the first phase and subsequent hypofractionation dose scheme in the second phase based upon different priority [planning target volume (PTV), clinical target volume (CTV) and organs at risk (OAR)] of display modes. METHODS: A case of carcinoma prostate was selected for demonstration. Varian Eclipse treatment planning system (TPS) was used for contouring and planning. In the first phase, a dose of 52 Gy in 26 fractions to the PTV and in the second phase, a dose of 19.5 Gy in 3 fractions to the PTV Boost was planned on the same CT data set. Both the plans (Phase 1 and Phase 2) were exported and processed using "Voxel-based radiobiology display (VRb) tool". Plan Sum for Biologically effective dose (BED)-Cube and equivalent dose of 2Gy (EQD2)-Cube was reconstructed using a combination of linear quadratic (LQ) and linear quadratic-linear (LQ-L) radiobiological models. Tumor control probability (TCP) and normal tissue complication probability (NTCP) for different target volumes and organs were also calculated using EQD2-volume histograms of the Plan Sum. RESULTS: An in-house graphical user interface (GUI) is developed to present the qualitative and quantitative evaluation of the multiphase treatment plans with different display modes and dose regimens. The voxel based TCP obtained for the combined target volume was 90.56%. NTCP for the bladder and rectum was calculated from the Plan Sum histograms and found to be 0.33% and ~0.0% respectively. CONCLUSION: The proposed methodology using the VRb tool offers superior plan evaluation for multiphase sequential radiotherapy treatment plans over the existing methods. ADVANCES IN KNOWLEDGE: PTV, CTV and OAR priority based display modes in VRb tool offers better understanding of radiobiological evaluation of sequential radiotherapy treatment plans.

Dosimetric comparison of dynamic conformal arc integrated with segment shape optimization and variable dose rate versus volumetric modulated arc therapy for liver SBRT.

PURPOSE: The aim is a dosimetric comparison of dynamic conformal arc integrated with the segment shape optimization and variable dose rate (DCA_SSO_VDR) versus VMAT for liver SBRT and interaction of various treatment plan quality indices with PTV and degree of modulation (DoM) for both techniques. MATERIAL: Twenty-five patients of liver SBRT treated using the VMAT technique were selected. DCA_SSO_VDR treatment plans were also generated for all patients in Monaco TPS using the same objective constraint template and treatment planning parameters as used for the VMAT technique. For comparison purpose, organs at risk (OARs) doses and treatment plans quality indices, such as maximum dose of PTV (Dmax%), mean dose of PTV (Dmean%), maximum dose at 2 cm in any direction from the PTV (D2cm%), total monitor units (MU's), gradient index R50%, degree of modulation (DoM), conformity index (CI), homogeneity index (HI), and healthy tissue mean dose (HTMD), were compared. RESULTS: Significant dosimetric differences were observed in several OARs doses and lowered in VMAT plans. The D2cm%, R50%, CI, HI and HTMD are dosimetrically inferior in DCA_SSO_VDR plans. The higher DoM results in poor dose gradient and better dose gradient for DCA_SSO_VDR and VMAT treatment plans, respectively. CONCLUSIONS: For liver SBRT, DCA_SSO_VDR treatment plans are neither dosimetrically superior nor better alternative to the VMAT delivery technique. A reduction of 69.75% MU was observed in DCA_SSO_VDR treatment plans. For the large size of PTV and high DoM, DCA_SSO_VDR treatment plans result in poorer quality.

Feasibility of 4D CT simulation with synchronized intravenous contrast injection in hepatocellular carcinoma.

BACKGROUND: Delivering Stereotactic Body Radiotherapy (SBRT) for Hepatocellular Carcinoma (HCC) is challenging mainly for two reasons: first, motion of the liver occurs in six degrees of freedom and, second, delineation of the tumor is difficult owing to a similar density of HCC to that of the adjoining healthy liver tissue in a non-contrast CT scan. To overcome both these challenges simultaneously, we performed a feasibility study to synchronize intravenous contrast to obtain an arterial and a delayed phase 4D CT. MATERIALS AND METHODS: We included seven HCC patients of planned for SBRT. 4D CT simulation was performed with synchronized intravenous contrast based on the formula TSCAN DELAY = T peak - (L0/Detector Coverage × Cine Duration in Seconds). This was followed by a delayed 4D CT scan. RESULTS: We found that, with our protocol, it is feasible to obtain a 4DCT with an arterial and a delayed phase making it comparable to a diagnostic multi-phase CT. The peak HU of the 4D scan and diagnostic CT were similar (mean peak HU 134.2 vs 143.1, p value = 0.58 N.S). Whereas in comparison with a non-contrast CT a significant rise in the peak HU was seen (mean peak 134.2 vs 61.4 p value = .00003). CONCLUSION: A synchronized contrast 4D CT simulation for HCC is safe and feasible. It results in good contrast enhancement comparable to a diagnostic 3D contrast CT scan.

Derivative-based gamma index: a novel methodology for stringent patient-specific quality assurance in the stereotactic treatment planning of liver cancer.

Objective:The development of a stringent derivative-based gamma (DBG) index for patient-specific QA in stereotactic radiotherapy treatment planning (SRTP) to account for the spatial change in dose.Methods:Twenty-five patients of liver SBRT were selected retrospectively for this study. Deliberately, two different kinds of treatment planning approaches were used for each patient. Firstly, the treatment plans were generated using a conventional treatment planning (CTP) approach in which the target was covered with a homogeneous dose along with the nominal dose fall-off around the treatment field. Subsequently, the other treatment plans were generated using an SRTP approach with the intent of heterogeneous dose within the target region along with a steeper dose gradient outside the treatment field as much as possible. For both kinds of treatment plans, two dimensional (2D) conventional gamma (CG) and DBG analysis were performed using the 2D ion chamber array and radiochromic film.Results:Difference in the DBG index was statistically significant whereas, for CG analysis, the difference in CG index was insignificant for both types of treatment plans (CTP and SRTP). A significant positive correlation was observed between the difference in the DBG index and the difference in HI for high gamma criteria.Conclusion:The DBG evaluation is found to be more rigorous, and sensitive to the only SRTP. The proposed method could be opted-in the routine clinical practice in addition to CG.Advances in knowledge:DBG is more sensitive to detect the spatial change of dose, especially in high dose gradient regions.

Voxel based BED and EQD2 Evaluation of the Radiotherapy Treatment Plan.

INTRODUCTION: Three-dimensional (3D) treatment planning of patient undergoing radiotherapy uses complex and meticulous computational algorithms. These algorithms use 3D voxel data of the patient to calculate the radiation dose distribution and display it over the CT image dataset for treatment plan evaluation. AIMS AND OBJECTIVE: The purpose of the present study is the development and implementation of radiobiological evaluation of the radiotherapy treatment plan incorporating the tissue-specific radiobiological parameters. MATERIAL AND METHOD: An indigenous program was written in MATLAB® software (version 2011b of Mathworks Inc.) to extract the patient treatment plan data from DICOM-RT files which are exported from the treatment planning system. CT-, Structures- and Dose-Cube matrices are reconstructed from the exported patient plan data. BED and EQD2 based dose volume histograms (DVHs), colorwash and iso-effective dose curves were generated from the physical Dose-Cube using the linear-quadratic (LQ) formalism and tissue-specific radiobiological parameters (α/ß). RESULTS AND CONCLUSION: BED-and EQD2-colorwash and iso-effective curves along with BED and EQD2 dose volume histograms provide superior radiobiological information as compared to those of physical doses. This study provides supplementary recipes of radiobiological doses along with the physical doses which are useful for the evaluation of complex radiotherapy treatment plan of the patients.